Certain chronic diseases destroy the functional cells in affected organs. Individuals with such diseases are often unable to produce proteins or other biological products necessary to maintain homeostasis and usually require numerous exogenous substances to survive. Transplanting healthy organs or cells into an individual suffering from such a disease may be necessary to save the individual's life. This type of therapy is generally regarded as a last alternative to curing an otherwise fatal condition. Such transplants, however, are often rejected by the body due to an immune response initiated in response to the foreign tissue or cells. Presently, the only recourse to combat this immune response is to administer chronic nonspecific immunosuppression agents. The use of nonspecific immunosuppression agents however, is fraught with unwanted side effects such as increased susceptibility to infection, hypertension, renal failure and tumor growth.
In the fields of cell and organ transplantation, Selawry et al., have demonstrated that Sertoli cells can be used to create an artificial privileged environment when isolated from the testes and then transplanted into heterologous sites. Privileged environments have been created using both allogeneic and xenogeneic Sertoli cells. Rajotte and Korbutt, 1997 Diabetes 46: 317-322. Similarly, both rat Sertoli cell allografts and porcine Sertoli cell xenografts have been shown to survive for at least two months in the rat brain without cyclosporin A immunosuppression. Saporta, S. et al., 1997 Exp. Neurology 146(2):299-304. Selawry, et al., have also demonstrated the immunoprotection of islet cells placed in the rat kidney capsule when cotransplanted with Sertoli cells. Long term islet survival and functional recovery in a diabetic rat model have been demonstrated. Selawry, H., et al., 1993 Cell Transplant 2:123-129. It has recently been suggested that Sertoli cells express an immunosuppressant factor, Fas ligand (Fas-L), responsible all or in part for providing the testis with its immunoprivileged status. Sandberg, P. R., et al., 1997 Cell Transplantation 6(2):191-193; Saporta, S., et al., supra.
Immune rejection of genetically altered cells during gene therapy also remains a problem. In order to overcome the problem, autologous cells, i.e., a patient's own cells, may be used. In fact, most of the currently approved human gene therapy protocols depend on genetic alteration of autologous cells. Such cells however, may be difficult to obtain due to the diseased state of the patient and are often destroyed during harvesting. Those cells that survive harvesting are often difficult to grow in vitro and require complicated culture conditions and purification methodologies.
There is a need, therefore, for compositions and methods for producing a biological factor in a subject wherein cells which are genetically altered to produce the biological factor are readily available and more easily manipulated in vitro. In addition, the need exists for compositions and methods for producing a biological factor in a subject who receives allogeneic or xenopeneic cells which do not trigger an immune response requiring chronic immunosuppression.